Too Early in PSA Era to See Drop in Prostate Cancer Mortality

Too Early in PSA Era to See Drop in Prostate Cancer Mortality

BOSTONMen are far more likely to be diagnosed with prostate
cancer today than 2 decades ago, and they have more aggressive treatment
options. Is their chance of dying of the disease dropping as a result? It is
too early in the era of prostate-specific antigen (PSA) testing to tell,
keynote speaker Michael J. Barry, MD, said at the 42nd Annual Meeting of the
American Society for Therapeutic Radiology and Oncology .

The incidence of prostate cancer has increased substantially,
and population-based mortality has dropped in the United States, said Dr.
Barry, chief of the General Medicine Unit, Massachusetts General Hospital, and
associate professor of medicine, Harvard Medical School.

Nonetheless, he cautioned that inconsistencies in everything
from testing procedures to treatment choices make comparison of outcomes from
observational studies impossible at this time. Only long-term controlled trials
can provide conclusive answers, he said: "I think we’ll see a
difference, but we need to prove it."

Dr. Barry cited unpublished results of an ongoing comparison of
prostate cancer outcomes between SEER areas in Seattle and Connecticut. These
two SEER areas had identical population-based prostate cancer mortality rates
in the pre-PSA era.

Seattle adopted PSA detection and aggressive treatment much
earlier and faster than Connecticut, according to Dr. Barry. His research
group, therefore, developed a
cohort study that
followed 100,000 Medicare-aged men in each area from 1987 on.

From 1987 to 1990, men in Seattle were twice as likely to be
diagnosed with prostate cancer and six times as likely to have a radical
prostatectomy as men in Connecticut, he said. The Seattle group also received
more radiation therapy.

With all that extra screening and treatment, Dr. Barry expected
to see an earlier effect on prostate cancer mortality in Seattle than in
Connecticut. "At least for 11 years, we haven’t seen it," he said.
"The age-adjusted prostate cancer mortality, the rate ratio, for both
areas is about 1.06actually with Seattle being a little higher, but not
significantly sothrough 11 years of follow-up."

Austrian Study

Dr. Barry contrasted these results with a preliminary report
from the state of Tyrol in Austria. An aggressive program of PSA screening and
cancer treatment in Tyrol has been credited with a 42% reduction in
population-based mortality in 1998 vs a base period of 1986 to 1990. The state
has 65,000 men, ages 45 to 75. It began its PSA testing program in 1993,
testing one third of the population the first year, and two thirds by 1996.

How could early detection produce such a large benefit if the
lead time for prostate cancer diagnosis in the PSA era is 8 years? he asked.
"I don’t fully understand these results, and I’m waiting for the paper
to be published," he said.

Four randomized trials in Europe and the United States are
collecting data on prostate cancer mortality, but Dr. Barry predicted that
"because of the slow progression of cancers being diagnosed now, it will
be years before we get results."

To dramatize the problems in comparing pre- and post-PSA
outcomes, he presented a 10-year nonrandomized comparison of outcomes from the
pre-PSA era, based on cases reported to SEER.

Cancer-specific survival for men with moderately differentiated
cancer was about 87% for radical prostatectomy, 76% for radiation, and 77% for
conservative therapy. "Do I think these figures represent a true
comparison?" he asked. "Absolutely not. We can’t make the
comparisons because of case selection."

He pointed to huge differences in overall survival rates in
these patients71% for radical prostatectomy, 48% for radiation, and 38% for
conservative therapy. "The healthier patients are getting radical
prostatectomy. The less healthy patients are getting radiation. The least
healthy patients are getting conservative therapy," he said, citing
differences in age, comorbidity, and other factors.

While praising several recent studies on treatment outcomes,
Dr. Barry concluded that post-PSA-era patients have not been followed long
enough to identify important predictors of outcomes. "It’s encouraging
to see good outcomes over 5 or 6 years, but, remember, in the pre-PSA era, many
of those patients wouldn’t have been diagnosed yet."

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